In the medical institution such as the hospitals, for the purpose of sterilizing tools to be used for surgery or treatment, (1) autoclave sterilization process, (2) ethylene oxide gas sterilization process, or (3) cold plasma sterilization process has been used.
On these sterilization processes, it is important 1) to distinguish whether the tool to be sterilized undergoes the sterilization steps or not; and 2) to detect whether the sterilization effect acting on the tool is proper or not.
Chemical indicators for the sterilization of which color tone are changed when subjected to sterilization have been used as one kind of means for the above mentioned distinguishment or detection, and these indicators should be used for their own specific sterilization method.
(Prior Art of the Indicator for Plasma Sterilization)
The cold plasma sterilization process which utilizes the bactericidal activity of the cold plasma of the oxidizing gas such as hydrogen peroxide gas is suitable for the sterilization of heat-sensitive medical tools, because the cold plasma sterilization process can be performed at a low temperature as in the case of the ethylene oxide gas sterilization process. Further, the cold plasma sterilization process has an advantage that the time required for the sterilization is shorter than the time for the ethylene oxide gas sterilization process.
As the typical cold plasma sterilization process which has been put to practical use until today, the “STERRAD” (registered trademark) which has been developed by Johnson & Johnson Co. (United States). The outline of sterilization step of this sterilization process is as follows, that is, after the inner area of a closed sterilizer is decompressed thoroughly, a constant amount of hydrogen peroxide are injected into the sterilizer and the hydrogen peroxide is allowed to vaporize, then a step where the substance to be sterilized is allowed to contact with the hydrogen peroxide steam for a prescribed time (about 8-16 minutes) and a following step where plasma of the hydrogen peroxide gas is generated by applying high frequency voltage are alternately repeated twice.
We, the inventors, have been already proposed chemical indicators to be used for the cold plasma sterilization process (Patent Literature 1 and Patent Literature 2).
The technological content of the above-mentioned Patent Literature 1 is the one which is related to an indicator which includes a basic dye such as triphenyl methane type, and a compound which has a mercapto group (discoloring assistant), and which is based on a principle that the color of the basic dye is brought into fading as a result of the oxidative decomposition of the basic dye owing to oxidation power of the hydrogen peroxide vapor or of the plasma formed from the hydrogen peroxide vapor.
Further, the content of Patent Literature 2 is the one which is related to an indicator which includes fluorane type colorless dye which has a lactone ring therein and which is used for the thermal recording paper, etc., and a compound which has a dithiocarbamil group (discoloring assistant), and which is based on a principle that the color of the dye is brought into changing as a result of the ring-opening of the lactone ring in the dye to change to a colored rhodamine dye owing to oxidation power of the hydrogen peroxide vapor or of the plasma formed from the hydrogen peroxide vapor.
In addition to the above mentioned indicator, as the indicator to be used for the cold plasma sterilization method, the followings have been also known:                the one which includes an anthraquinone type dye which has an amino group (Patent Literature 3);        the one which includes a pigment which comprises an anthraquinone type compound as a main ingredient and an organic amine type compound (Patent Literature 4);        the one which includes a compound capable of changing its color tone in accordance with the pH variation (Patent Literature 5);        the one which includes a compound selected from the group consisting of adsorption indicators and chelate titration/metal indicators, and an organic metallic compound (Patent Literature 6);        the one which includes a substance of which color is changed by radicals generated when hydrogen peroxide plasma sterilization is performed, such as light green SF yellow, Guinea Green, brilliant green, etc. (Patent Literature 7);        the one which includes (a) adsorption indicator, chelate titration/metal indicator (e.g., hematoxylin, etc.), (b) organic metallic compound, and (c) poly polyhydric alcohol (Patent Literature 8)        the one which includes (a) at least one of anthraquinone type dyes, azo dyes, and methine type dyes; (b) nitrogenous polymer (e.g., polyamide resin, etc.), and (c) cationic surfactant (Patent Literature 9); and        the one which includes (a) at least one of styrene-acrylic resins or styrene-maleic resins, and (b) methine type dye (Patent Literature 10).(Prior Art of the Indicator for Ethylene Oxide Gas Sterilization)        
Specific azo dyes used for plasma sterilization according to the present invention are the ones which are known in the art of preparation of indicator for ethylene oxide gas sterilization. As for indicators for ethylene oxide gas sterilization which use such azo dyes, numerous technologies have been already known. Patent Literatures 11-19 may be enumerated as known examples.
In the technology concerning the indicator for the ethylene oxide gas sterilization, the one described in the above mentioned Patent Literature 11 is a principal technique, and the remainder are primarily related to the improving or modifying techniques for the former principal technique.
A viewpoint common to the above mentioned known techniques is that an azo dye which possesses a heterocyclic ring which includes a tertiary nitrogen atom and an appropriate acidic material (decoloring accelerant to promote the reaction of the azo dye and the ethylene oxide) are coated or printed onto a substrate such as paper with the aid of a binder, and the color tone of the obtained indicator is brought into changing to another color tone as a result that the azo dye undergoes an ring-opening addition reaction with ethylene oxide (i.e., ethylene oxide is added to the tertiary nitrogen atom in the heterocyclic ring of the azo dye, and thereby allowing the nitrogen atom to change to quaternary form), and thereby the azo dye is brought into changing to a kind of cationic dye, when the ethylene oxide gas sterilization is performed.
All of the indicators for ethylene oxide gas sterilization which are prepared in accordance with any of the above mentioned techniques hardly discolor upon the cold plasma sterilization process which uses hydrogen peroxide gas or the like.
(Prior Art of the Indicator for Heat Sterilization)
With respect to a specific azo dye which may be used in the indicator for plasma sterilization according to the present invention, an indicator for heat sterilization which is based on a principle that the color of the specific azo dye is brought into changing as a result of reaction of the azo dye with an epoxy compound under the presence of an acidic catalyst has been proposed (Patent Literature 20).
In this indicator, the azo dye and the epoxy compound are mutually separately held in their individual layers via an isolation membrane, and the indicator is based on a principle that its color is changed when the isolation membrane is melted by heat or high pressure steam and thereby the azo dye and the epoxy compound is brought into contacting and reacting with each other.
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